Many naturally occurring substituted anthraquinones and naphthoquinones possess cytotoxic antileukemic activities (Zee-Cheng P. et al., J. Med. Chem. 1979, 22, 501-505; Chang, P., Lee, K. H. Phytochemistry. 1984, 23, 1733-1736; T. Hayashi, F. Smith, and K. H. Lee, K. H. J. Med. Chem. 1987, 30, 2005-2008). In addition, the natural furanonaphthoquinones 1 and 2 and their synthetic analog 3 (see figures below) show potent cytotoxicity against KB cells with ED.sub.50 values of 1.0, 2.0, and 0.3 .mu.g/mL, respectively (Rao, M. M.; Kingston, D. G. I. J. Nat. Prod. 1982, 45, 600-604).
The unsubstituted thiophene derivative naphtho[2,3-b]thiophene-4,9-dione (4) also was found to be cytotoxic against KB cells with an ED.sub.50 value of 1.4 .mu.g/mL (Goncalves, R.; Brown, E. V. J. Org. Chem. 1952, 17, 698-704; Weinmayr, V. U.S. Pat. No. 2,497,334 1950; Weinmayr, V. J. Am. Chem. Soc. 1952, 74, 4353-4357; Carruthers, W.; Douglas, A. G.; Hill, J. J. Chem. Soc. 1962, 704-708; Carruthers, W. J. Chem. Soc. 1963, 4477-4483; Tagawa, H.; Ueno, K. Chem. Pharm. Bull. 1978, 26, 1384-1393; Huang, L. J.; Kuo, S. C.; Perng, C. Y.; Chao, Y. H.; Wu, T. S.; McPhail, A. T.; Cheng, H. H.; Lee, K. H. Bioorg & Med. Chem. Letters, submitted.) Introduction of a lipophilic acetyl group gave 2-acetyl naphtho[2,3-b]thiophene-4,9-dione (5) with enhanced cytotoxicity (ED.sub.50 =0.4 .mu.g/mL)(Huang, L. J.; Kuo, S. C.; Perng, C. Y.; Chao, Y. H.; Wu, T. S.; McPhail, A. T.; Cheng, H. H.; Lee, K. H. Bioorg & Med. Chem. Letters, submitted).